'Tamed' Polio Virus Kills Neuroblastoma Cells in Mice

STONY BROOK, N.Y., March 16 -- The polio virus has been put to work at killing neuroblastoma cells in mice.

A highly attenuated version of the polio virus killed neuroblastoma tumors even when the animals were previously immunized against wild-type polio, according to Hidemi Toyoda, M.D., Ph.D., of the State University of New York at Stony Brook.

Moreover, the cured animals were resistant to attempts to re-establish neuroblastoma through the transplant of cancer cells, Dr. Toyoda and colleagues reported in the March 15 issue of Cancer Research.

The finding may represent a step forward in the treatment of neuroblastoma, one of the most common cancers of childhood and one for which prognosis is poor, Dr. Toyoda and colleagues said.

"A tamed poliovirus represents a significant step in finding viral treatments that can kill tumors without harming patients," Dr. Toyoda said in a statement. "Effectively, we have harnessed a virus that was deadly in children just a few decades ago, namely polio, and used an essential aspect of its nature to destroy a disease that is deadly today."

The work builds on research by Eckard Wimmer, Ph.D., also of Stony Brook, who in 2002 was the first to synthesize the polio virus from its chemical constituents.

Dr. Wimmer, a senior author of this study, also showed that a point mutation in a "spacer" region of the virus weakened it by a factor of 10,000, alleviating fears that it could cause disease.

For this study, he and colleagues made other changes in the virus to stabilize the point mutation during replication, so that descendant virions cannot recover their disease-causing capability.

However, the "tamed" virus retains its ability to infect and kill neuroblastoma cells, Dr. Toyoda and colleagues reported.

The researchers developed transgenic mice that were susceptible to polio infection and then immunized them against the disease. They were then injected with neuroblastoma cells bearing the CD155 receptor used by the virus.

After about a week -- when the mean tumor volume had reached about 170 cubic millimeters -- the mice were randomized and injected intratumorally with a saline solution or the attenuated poliovirus on four consecutive days.

Eight days later, the tumors in all of the control mice had grown to more than 17 millimeters in diameter, but those in the treated animals had regressed and the average tumor volume was 128 cubic millimeters.

Importantly, Dr. Toyoda and colleagues said, none of the treated animals showed signs of paralysis.

While nine of the 11 treated animals had complete regression by day 180, two did not, the researchers said, and re-injection with the polio virus had no effect.

Mice with no evidence of recurrent tumors at six months were re-challenged with the same dose of neuroblastoma cells, this time injected into the opposite flank, Dr. Toyoda and colleagues said.

None of the animals developed tumors at the injection site or elsewhere, they reported.

"This immunity against neuroblastoma acquired by the animals is still something of a mystery, one that we hope to address in future studies," Dr. Toyoda said. "But it is an encouraging sign since neuroblastoma are known to relapse quite frequently."